ABSTRACT The dentate gyrus in the hippocampus is one of two brain regions with lifelong neurogenesis in mammals. Despite an increasing amount of information about the characteristics of the newborn granule cells, the specific contribution of their robust generation to memory formation by the hippocampus remains unclear. We describe here a possible role that this population of young granule cells may have in the formation of temporal associations in memory. Neurogenesis is a continuous process; the newborn population is only composed of the same cells for a short period of time. As time passes, the young neurons mature or die and others are born, gradually changing the identity of this young population. We discuss the possibility that one cognitive impact of this gradually changing population on hippocampal memory formation is the formation of the temporal clusters of long-term episodic memories seen in some human psychological studies.

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The aims of the paper are to update Rolls' quantitative computational theory of hippocampal function and the predictions it makes about the different subregions (dentate gyrus, CA3 and CA1), and to examine behavioral and electrophysiological data that address the functions of the hippocampus and particularly its subregions. Based on the computational proposal that the dentate gyrus produces sparse representations by competitive learning and via the mossy fiber pathway forces new representations on the CA3 during learning (encoding), it has been shown behaviorally that the dentate gyrus supports spatial pattern separation during learning. Based on the computational proposal that CA3-CA3 autoassociative networks are important for episodic memory, it has been shown behaviorally that the CA3 supports spatial rapid one-trial learning, learning of arbitrary associations where space is a component, pattern completion, spatial short-term memory, and spatial sequence learning by associations formed between successive items. The concept that the CM recodes information from CM and sets up associatively learned back-projections to neocortex to allow subsequent retrieval of information to neocortex, is consistent with findings on consolidation. Behaviorally, the CM is implicated in processing temporal information as shown by investigations requiring temporal order pattern separation and associations across time; and computationally this could involve associations in CM between object and timing information that have their origins in the lateral and medial entorhinal cortex respectively. The perforant path input from the entorhinal cortex to DG is implicated in learning, to CA3 in retrieval from CM, and to CA1 in retrieval after longer time intervals ("intermediate-term memory") and in the temporal sequence memory for objects.

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Interaction of astrocytes and microglia is an important factor of the development of neuroinflammation because impairment of the mechanisms of this neuroprotective interaction may underlie the progression of neuropathology. We studied the changes in cell populations of astro- and microglia in the rodent hippocampus after intraperitoneal injection of bacterial lipopolysaccharide (LPS). Chronic administration of LPS elevated the number of microglial cells in the hilus of the dentate gyrus of the mouse hippocampus, whereas a single injection of a cumulative dose of LPS (5 mg/kg) did not induce a similar response. In rats, a single injection of LPS decreased the number of astrocytes in the hilus of the dentate gyrus of the hippocampus. We believe that in the hippocampus, in the cerebral structure, which is selectively vulnerable to neuroinflammation, glial cells of the dentate hilus are most responsive under the conditions of neuroinflammation induced by systemic administration of LPS.

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